Activation of the immune system of vertebrates is an important mechanism for protecting animals against pathogens and malignant tumors. The immune system consists of many interacting components including the humoral and cellular branches. Humoral immunity involves antibodies that directly bind to antigens. Antibody molecules as the effectors of humoral immunity are secreted by B lymphocytes. Cellular immunity involves specialized cytotoxic T lymphocytes (CTLs), which recognize and kill other cells and produce non-self antigens. CTLs respond to degraded peptide fragments that appear on the surface of the target cell bound to MHC (major histocompatibility complex) class I molecules. It is understood that proteins produced within the cell are continually degraded to peptides as part of cellular metabolism. These fragments are bound to the MHC molecules and are transported to the cell surface. Thus the cellular immune system is constantly monitoring the spectra of proteins produced in all cells in the body and is poised to eliminate any cells producing non-self antigens.
Vaccination is the process of priming an animal for responding to an antigen. The antigen can be administered as a protein (classical) or as a gene, which then expresses the antigen (genetic immunization). The process involves T and B lymphocytes, other types of lymphoid cells, as well as specialized antigen presenting cells (APCs), which can process the antigen and display it in a form which can activate the immune system. Current modes for the administration of genetic vaccines have focused on invasive procedures, which include injection by needles, scarification, and gene gun-mediated penetration. Inoculation using invasive techniques requires equipment and personnel with special medical training, and is usually associated with discomfort and potential hazards (e.g., bleeding, infection).
The efficacy of a vaccine is measured by the extent of protection against a later challenge by a tumor or a pathogen. Effective vaccines are immunogens that can induce high titer and long-lasting protective immunity for targeted intervention against diseases after a minimum number of inoculations. For example, genetic immunization is an approach to elicit immune responses against specific proteins by expressing genes encoding the proteins in an animal's own cells. The substantial antigen amplification and immune stimulation resulting from prolonged antigen presentation in vivo can induce a solid immunity against the antigen. Genetic immunization simplifies the vaccination protocol to produce immune responses against particular proteins because the often difficult steps of protein purification and combination with adjuvant, both routinely required for vaccine development, are eliminated. Since genetic immunization does not require the isolation of proteins, it is especially valuable for proteins that may lose conformational epitopes when purified biochemically. Genetic vaccines may also be delivered in combination without eliciting interference or affecting efficacy, which may simplify the vaccination scheme against multiple antigens.
Noninvasive approaches to administering vaccines have been investigated. For example, topically-applied protein-based vaccines have been studied (Glenn et al., “Skin immunization made possible by cholera toxin,” Nature 391:851, 1998); however, their usefulness is limited. The efficacy of genetic vaccines is in general superior to that of protein vaccines due to the de novo synthesis of antigens similar to natural infections (McDonnell and Askari, “DNA vaccines,” New Engl J Med 334:42-45, 1996).
As described above, vaccination usually requires equipment, e.g., syringe needles or a gene gun, and special skill for the administration of the vaccine. There is a great need and desire in the art for the inoculation of vaccines by personnel without medical training and equipment. A large number of diseases could potentially be immunized against through the development of noninvasive vaccination because the procedure is simple, effective, economical, painless, and potentially safe. As a consequence, noninvasive vaccination may boost vaccine coverage in developing countries where medical resources are in short supply, as well as in developed countries due to patient comfort. Infectious diseases caused by (1) viruses, including AIDS and flu, (2) bacteria, including tetanus and TB, (3) parasites, including malaria, and (4) malignant tumors, including a wide variety of cancer types may all be prevented or treated with noninvasive vaccines without requiring special equipment and medical personnel. The compositions, devices, and methods described herein address this longstanding need.